Composition for sustained release of human growth hormone

• US 6,051,259 A
• Filed: 02/19/1999
• Issued: 04/18/2000
• Est. Priority Date: 12/02/1992
• Status: Expired due to Fees

• Current Assignee: Alkermes Controlled Therapeutics Inc. II (Alkermes plc)
• Original Assignee: Alkermes Controlled Therapeutics Inc. II (Alkermes plc)
• Inventors: Khan, M. Amin, Bernstein, Howard, Johnson, OluFunmi Lily, Ganmukhi, Medha M., Auer, Henry
• Primary Examiner(s): AZPURU, CARLOS A
• Application Number:
  US09/252,746
• Time in Patent Office: 424 Days
• Field of Search: 424/502, 424/423, 424/426, 424/489, 424/499, 424/500, 424/501, 514/21, 530/399, 530/839
• US Class Current: 424/502
• CPC Class Codes: A61K 38/27 Growth hormone [GH], i.e. somatotropin
• CPC Class Codes: A61K 9/1611 Inorganic compounds
• CPC Class Codes: A61K 9/1647 Polyesters, e.g. poly(lactide-co-glycolide)
• CPC Class Codes: A61K 9/1694 resulting in granules or microspheres of the matrix type containing more than 5% of excipient
• CPC Class Codes: B82Y 5/00 Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
• CPC Class Codes: Y10S 530/839 Nerves; brain
• CPC Class Codes: Y10T 428/2985 Solid-walled microcapsule from synthetic polymer

Abstract

The method of the invention for producing a composition for the sustained release of biologically active hGH includes dissolving a biocompatible polymer in a polymer solvent to form a polymer solution, dispersing particles of biologically active, metal cation-stabilized hGH in the polymer solution, and then solidifying the polymer to form a polymeric matrix containing a dispersion of said hGH particles.

Claims

1. A composition for the sustained release of human growth hormone from a polymer matrix comprising:

a) poly(lactide-co-glycolide); and

b) particles of zinc-complexed human growth hormone, with a zinc cation component-to-human growth hormone molar ratio between about 4;

1 and about 100;

1, wherein said particles are dispersed within the poly(lactide-co-glycolide) and wherein the proportion of human growth hormone in the sustained release composition is between 10 and 30 weight percent.

2. The composition of claim 1 wherein the zinc cation component-to-human growth hormone molar ratio is about 10:

1.

3. The composition of claim 2 further comprising a second metal cation component, wherein the second metal cation component is not complexed to said human growth hormone, and wherein the second metal cation component is dispersed within the polymer matrix at a concentration of at least about 1% by weight of polymer.

4. The composition of claim 1 wherein the poly(lactide-co-glycolide) has a lactide:

glycolide ratio of 1;

1.

5. The composition of claim 4 wherein the poly(lactide-co-glycolide) is unblocked.

6. The composition of claim 5 wherein the molecular weight of the poly(lactide-co-glycolide) is about 6,000 to about 31,000 Daltons.

7. A method of delivering human growth hormone to a subject in need thereof comprising the step of administering to said subject a composition for the sustained release of human growth hormone comprising:

a) poly(lactide-co-glycolide); and

b) particles of zinc-complexed human growth hormone, with a zinc cation component-to-human growth hormone molar ratio between about 4;

1 and about 100;

1, wherein said particles are dispersed within the poly(lactide-co-glycolide) and wherein the proportion of human growth hormone in the sustained release composition is between 10 and 30 weight percent.

8. The method of claim 7 wherein the zinc cation component-to-human growth hormone molar ratio is about 10:

1.

9. The method of claim 8 further comprising a second metal cation component, wherein the second metal cation component is not complexed to said human growth hormone, and wherein the second metal cation component is dispersed within the polymer matrix at a concentration of at least about 1% by weight of polymer.

10. The method of claim 7 wherein the poly(lactide-co-glycolide) has a lactide:

glycolide ratio of 1;

1.

11. The method of claim 10 wherein the poly(lactide-co-glycolide) is unblocked.

12. The method of claim 11 wherein the molecular weight is about 6,000 to about 31,000 Daltons.